| BackgroundChronic obstructive pulmonary disease(COPD),a mainly respiratory disease in“the Healthy China 2030 Initiative Action Plan",has a high prevalence and death rate in China.The disease is characterized by ongoing incomplete reversible airflow limitation and persistent respiratory symptoms.Symptoms management are the more important part of COPD management.Symptoms are the leading cause for seeking healthcare in patients with COPD.These symptoms interact with each other and form symptom clusters.The term symptom cluster consisting of at least 2 or more interrelated symptoms that may indicate a common etiology or mechanism.Compared with individual symptom,the complicated and synergistic detrimental relationship between multiple symptoms leads to a higher disease burden,poorer quality of life,and shorter survival.An understanding of symptom cluster of patients could help clinicians develop more comprehensive and useful assessment tools,as well as more targeted and effective interventions.Identifying the symptom clusters of patients with COPD and analyzing their stability can strengthen the symptom management,exploring the intercorrelation mechanism of symptoms within the clusters,and provide a more certain theoretical basis for optimizing symptom management strategies.At the same time,in view of the differences between individuals in physical conditions,self-management and treatment compliance,different individuals also have heterogeneity in the severity of symptom clusters.Exploring the heterogeneous development trajectory of different symptom clusters and its influencing factors can lay the foundation for accurate care of COPD.However,current studies on COPD symptom clusters are all crosssectional designs.Measuring clusters of symptoms at a single point in time makes it difficult to verify their stability and identify the different types of development paths.In this study,a longitudinal study design was adopted to explore the composition of symptom groups at multiple time points and verify their stability.Furthermore,the latent variable growth mixed model was adopted to find out the trajectory of different types of symptom groups in COPD patients and their influencing factors.In order to reveal the internal mechanism of symptom groups in COPD patients and optimize symptom management strategies,Screening and intervention of patients with high-risk symptom cluster locus provide valuable reference indicators.At the same time,considering that acute exacerbation is the main cause of death and hospitalization in COPD patients,and symptom groups are the most direct and sensitive indicators of disease changes,this study will also try to take symptom groups and trajectories as new indicators to explore their predictive effect on acute exacerbation,providing new ideas for expanding research in this field.Objective1.Describe the prevalence and severity of the common symptoms in COPD,and to explore the number,types,and stability of symptom clusters in COPD;2.Identification of heterogeneous development trajectories of stable symptom clusters,and its influencing factors through demographic data,characteristics of disease and individual.3.Analyzing the predictive effect of heterogeneous development trajectories of COPD symptom cluster locus on acute exacerbation.MethodsUsing convenience sampling,A total of 371 patients were recruited from 8 communities and 6 hospitals in Jinan from March to December 2019 to conduct an exploratory study on symptom clusters.A total of 276 patients were recruited from 11 other communities in Jinan from March to July 2021 to conduct external validation for the stability of the symptom clusters;Then,a longitudinal study was conducted,with follow-up visits every 6 months and a total of 2 times.The data were used to further verify the stability of development trajectories of the symptom cluster,analyze the heterogeneous development trajectories and influencing factors of the stable symptom cluster,and the predictive effect of the development heterogeneous trajectories of the symptom cluster on acute exacerbation.The Medical Research Council Standard Dyspnea Scale(mMRC)was used to assess symptoms of dyspnea.Symptoms of cough,sputum,chest tightness,and shortness of breath were assessed using the first four items of the COPD Assessment Scale(CAT).The Generalized Anxiety Scale(GAD-2)was used to assess the anxiety of the patients in the past two weeks.Patients’ depression symptoms were evaluated using the simple version of the patient Health Questionnaire(PHQ-2).The Manchester COPD Fatigue Scale(MCFS)and the Chronic Disease Treatment-Fatigue Function Assessment Scale(FACIT-F)were used to evaluate the fatigue symptoms of the patients.The Athens Insomnia Scale(AIS)and the Pittsburgh Sleep Quality Index(PSQI)were used to evaluate the patients’ sleep quality.Data analysis SPSS 26.0,Mplus 8.3 and Stata 17.0 were used for data analysis.Descriptive analysis was used to report the socio-demographic data,disease and individual characteristics,symptom incidence and severity in patients with COPD.Exploratory factor analysis was performed to determine the numbers and components of symptom clusters based on severity ratings at each time point.Univariate repeated measure analysis of variance was used to examine the difference in severity of the same symptom cluster at different time points.The latent growth model was used to analyze the general development trends of symptom clusters.The growth mixture model was used to analyze the development trajectories of stable symptom clusters.Binomial logistic regression and polynomial logistic regression were used to analyze the influencing factors of the development trajectories.Negative binomial regression and zeroexpansion Poisson regression model were used to analyze the predictive effect of development trajectories on exacerbation in patients with COPD.Result1.There were three symptom clusters in patients with COPD.Principle of optimal number of symptom cluster were:each symptom cluster contains at least two symptoms,Eigenvalues were greater than 1,accounting for 60%of the total variance,factor loadings were greater than 0.4,and indicating a good fit between the data and the model.Cronbach’s alpha coefficients of above 0.6,the Average Variance Extracted is above 0.5,and greater than the correlation coefficient between symptom clusters,indicating that the three symptom clusters are valid and have good internal consistency and discrimination validity.According to the core symptoms,three symptom cluster namely cough-sputum symptom cluster,respiratory-related symptom cluster and emotional-related symptom cluster,respectively.2.Each symptom cluster had different heterogeneous development trajectories.①The cough-sputum symptom cluster has two heterogeneous development trajectories,namely mild cough-sputum trajectory(91.7%),and severe cough-sputum trajectory(8.3%),respectively.The results of multiple logistic regression suggested that,compared with the mild coughsputum trajectory,female(OR=0.150,P=0.033),living in rural area(OR=0.205,P=0.004),summer(OR=0.069,P=0.005),and autumn(OR=0.105,P=0.012),overweight patients with BMI≥24.0 Kg/m2(OR=7.993,P=0.016)were statistically significant predictors of severe cough-sputum symptom cluster trajectory;②The respiratory-related symptoms cluster also had two trajectories,namely low-stable trajectory(81.6%),and high-improving trajectory(18.4%),respectively.The results of multiple logistic regression suggested that,compared with the lowstable trajectory,BMI<18.5 Kg/m2(OR=10.310,P=0.010),and comorbidities(OR=1.460,P=0.005)were statistically significant predictors of the high-improving trajectory;③The emotional-related symptom cluster has three trajectories,namely the emotional improvement trajectory(33.8%),the emotional stability trajectory(58.7%),and the emotional deterioration trajectory(7.5%),respectively.The results of multiple logistic regression suggested that,using the stability trajectory as reference,current smoking(OR=2.580,P=0.023)was the predictive factor of the emotional improvement trajectory,autumn(OR=4.321,P=0.035)was statistically significant predictors of the emotional deterioration trajectory.3.The results of trajectories predicting acute exacerbation and hospitalization were as follows:① Taking mild cough-sputum trajectory as reference,the severe cough-sputum trajectory was associated with an increased risk of exacerbation(adjusted incidence rate ratio[IRR],2.06;95%confidence interval,1.29～3.26).② Taking the emotional stability trajectory as reference,the emotional improvement trajectory was associated with a decreased risk of exacerbation(adjusted incidence rate ratio[IRR],0.57;95%confidence interval,0.42～0.79);the emotional deterioration trajectory was associated with an increased risk of exacerbation(adjusted incidence rate ratio[IRR],1.77;95%confidence interval,1.13～2.76).③Taking emotional stability trajectory as reference,the emotional deterioration trajectory was associated with an increased risk of hospitalization(adjusted incidence rate ratio[IRR],5.69;95%confidence interval,2.49～13.01).④ There was no statistically significant between respiratory-related symptom cluster and acute exacerbation.Conclusion1.In this study,three stable symptom clusters consisting of 9 symptoms were identified in patients with stable COPD,including respiratory-related symptom cluster with dyspnea,chest tightness and breathlessness as the core symptoms,cough-sputum symptom cluster with cough and sputum as the core symptoms,and emotional-related symptom cluster with anxiety and depression as the core symptoms.An understanding of symptom cluster of patients could help clinicians develop more comprehensive and targeted and effective interventions.2.The three types of stable symptom clusters have different trajectories,and the trajectories of symptom clusters are affected by corresponding high risk factors.Being female,living in rural areas,summer and autumn are were negatively correlated with severe coughsputum symptom cluster trajectory,and overweight patients with higher BMI is positively associated with severe cough-sputum symptom cluster trajectory,Low BMI and comorbidities were positively associated with high-improving trajectory of respiratory-related symptom cluster;Current smoking and autumn were positively associated with the emotional deterioration trajectory.For patients with these characteristics,targeted interventions can be implemented to alleviate or reduce the burden of symptoms and improve the quality of life of patients.3.The severe cough-sputum symptom cluster trajectory,the emotional improvement trajectory,and the emotional deterioration trajectory was associated with exacerbation.The severe cough-sputum symptom cluster trajectory,and the emotional deterioration trajectory were associated with an increase of exacerbation in patients of COPD.the emotional improvement trajectory was associated with a decrease of exacerbation in patients of COPD.The emotional deterioration trajectory was associated with an increase of hospitalization.This suggests that we should design a more concise symptom assessment scale suitable for selfmonitoring of patients with COPD at home,and dynamically monitor and manage symptom groups. |
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